Protein Biomarkers and Host RNA Expression Profiles in Congenital Cytomegalovirus Infection
調査の概要
状態
詳細な説明
Background:
Human cytomegalovirus (CMV) is one of the most common causes of congenital viral infection, leading to a significant number of children with permanent disabilities. It is recognized as the major infectious cause of sensorineural hearing loss (SNHL) and neurodevelopmental abnormalities in infants. Its pathogenesis is largely unknown due to the complex interplay between viral, maternal, placental, and child factors. In Western Europe the incidence is estimated to 0.5-0.7% of all live births. In Denmark there are 240-480 children born every year with CMV infection, but the incidence has not been studied since 1979. Among the congenitally infected infants, approximately 10% are estimated to have symptoms at birth, ranging from mild, such as petechiae, to severe, such as microcephaly. Approximately half of these symptomatic children develop permanent long-term disabilities, such as hearing loss, cognitive and motor developmental delay. Asymptomatic children are also at risk for CMV-related disabilities, and 10-15% will develop SNHL. SNHL after congenital CMV infection may be present at birth or occur later in childhood and therefore, a significant part of these will not be detected in time for diagnosis and appropriate treatment, e.g., ganciclovir within the first 30 days of life. At present, there is no reliable virological marker to determine which infants will develop sequelae.
Method:
A nationwide retrospective case-control study of all neonates with congenital CMV infection in Denmark from 2010 through 2025. DBS samples will be obtained from the Danish Neonatal Screening Biobank, Statens Serum Institut. Proteomic analyses and RNA sequencing will be performed at the Department for Congenital Disorders, Statens Serum Institut. Cases will be randomly assigned to a "Discovery cohort" and compared to a control group of neonates matched on gestational age, sex, birthweight and age at DBS sample collection.
Perspectives:
New molecular-based diagnostic tools may contribute to improve early diagnosis and treatment of infants with congenital CMV infection and potentially prevent development of sequelae. Additionally, understanding of the pathogenesis at a molecular level of severe disease manifestations of the disease, could form the basis for development of novel interventions for better prevention and treatment.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Kia Hee Schultz Dungu, MD
- 電話番号：+45 22645782
- メール：kia.hee.schultz.dungu@regionh.dk
研究連絡先のバックアップ
- 名前：Ulrikka Nygaard, Ass Prof PhD
- 電話番号：+45 35459761
- メール：Ulrikka.Nygaard@regionh.dk
研究場所
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Copenhagen、デンマーク、2100
- 募集
- Department of Paediatrics and Adolescent Medicine, Rigshospitalet
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コンタクト：
- Kia Hee Schultz Dungu, MD
- 電話番号：+45 22645782
- メール：kia.hee.schultz.dungu@regionh.dk
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Copenhagen、デンマーク、2300
- 募集
- Department of Congenital Disorders, Statens Serum Institut
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コンタクト：
- David M Hougaard, D.Sc (med)
- 電話番号：+45 32683544
- メール：dh@ssi.dk
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参加基準
適格基準
就学可能な年齢
- 子
健康ボランティアの受け入れ
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Children born between 1 January 2010 and 31 December 2025 with an available neonatal dried blood spot sample collected through the Danish National Newborn Screening Program.
- Cases: children with verified congenital CMV infection, defined as a positive CMV PCR result on neonatal dried blood spot, blood, or urine collected within the neonatal period.
- Controls: children without evidence of congenital CMV infection selected from the same newborn screening population and matched to cases on sex, gestational age, birthweight, and age at DBS sampling.
Exclusion Criteria:
- DBS samples not approved for research use.
- DBS samples with insufficient blood material for RNA expression profiling and/or proteomic analyses.
- Samples with inadequate analytical quality for molecular or proteomic analyses.
研究計画
研究はどのように設計されていますか？
デザインの詳細
コホートと介入
グループ/コホート |
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Cases
300 children with symptomatic congenital CMV infection. Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis. |
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Control group 1
300 children without congenital CMV infection. Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis. |
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Control group 2
30 neonates with asymptomatic congenital CMV infection and no sequelae Study procedures: Diagnostic/prognostic test and disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses. Cases will be randomly assigned to a "Discovery Cohort" for identification of diagnostic/prognostic RNA and proteomic profiles). Disease pathogenesis: Host RNA expression profiling by RNA sequencing and proteomic analyses will be performed to explore disease pathogenesis. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Differential protein expression associated with sequelae following congenital cytomegalovirus infection
時間枠：At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Normalized protein expression levels measured by Olink proteomics in neonatal dried blood spot samples obtained at birth from children with congenital cytomegalovirus infection who subsequently developed sequelae compared with children who did not develop sequelae and healthy controls.
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At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Differential host RNA expression associated with sequelae following congenital cytomegalovirus infection
時間枠：At neonatal dried blood spot sampling (typically 2-3 days after birth).
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Host RNA expression profiles measured in neonatal dried blood spot samples obtained at birth from children with congenital cytomegalovirus infection who subsequently developed sequelae compared with children who did not develop sequelae and healthy controls.
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At neonatal dried blood spot sampling (typically 2-3 days after birth).
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Immune pathway enrichment based on proteomic and RNA expression profiles
時間枠：At neonatal dried blood spot collection (typically 2-3 days after birth).
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Immune and inflammatory pathways will be assessed by host RNA expression and normalized protein expression levels measured in neonatal dried blood spot samples.
Pathway enrichment analyses will be used to identify biological pathways associated with congenital cytomegalovirus infection and subsequent sequelae.
Exploratory comparisons will be made with previously published host RNA expression signatures related to infectious disease and immune responses.
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At neonatal dried blood spot collection (typically 2-3 days after birth).
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Kia Hee Schultz Dungu, MD、Rigshospitalet, Denmark
- スタディチェア：Ulrikka Nygaard, Ass Prof PhD、Rigshospitalet, Denmark
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- H-21009288-CMV
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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